Title:
COMPOSITION FOR PREVENTION OR TREATMENT OF LIVER CANCER, COMPRISING MODIFIED RT-LET7 AS ACTIVE INGREDIENT
Document Type and Number:
WIPO Patent Application WO/2023/013990
Kind Code:
A1
Abstract:
The present invention relates to a pharmaceutical composition for prevention or treatment of liver cancer, comprising, as an active ingredient, modified RT-LET7 or modified RT-LET7 with which a liver cell-targeted moiety is combined, and compared to a conventional RT-LET7, which is antisense microRNA (AS-miRNA) for inhibiting Let-7i-5p, the modified RT-LET7 according to the present invention increases the inhibition of Let-7i-5p expression, increases the inhibition of liver cancer cell growth, increases TSP1 expression, and increases phagocytosis activity of macrophages. In addition, the liver cell-targeted moiety is combined with the modified RT-LET7 so as to improve delivery liver cancer cells and remarkably improve the effectiveness of liver cancer treatment, and thus the modified RT-LET7 can be effectively used in a pharmaceutical composition for prevention or treatment of liver cancer, or as a checkpoint inhibitor for prevention or treatment of CD47-positive liver cancer.
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Inventors:
NAM SUK-WOO (KR)
YANG HEE-DOO (KR)
YANG HEE-DOO (KR)
Application Number:
PCT/KR2022/011190
Publication Date:
February 09, 2023
Filing Date:
July 29, 2022
Export Citation:
Assignee:
NEORNAT (KR)
International Classes:
C12N15/113; A61K31/7088; A61K48/00; A61P35/00
Domestic Patent References:
| WO2012119051A2 | 2012-09-07 |
Foreign References:
| KR20200119538A | 2020-10-20 |
Other References:
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CUI HAO, ZHU XINYING, LI SHUYUE, WANG PEIPEI, FANG JIANPING: "Liver-Targeted Delivery of Oligonucleotides with N-Acetylgalactosamine Conjugation", ACS OMEGA, ACS PUBLICATIONS, US, vol. 6, no. 25, 29 June 2021 (2021-06-29), US , pages 16259 - 16265, XP055873459, ISSN: 2470-1343, DOI: 10.1021/acsomega.1c01755
AHN J, FLAMM SL HEPATOCELLULAR CARCINOMA DIS MON, vol. 50, 2004, pages 556 - 573
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BRUIX J ET AL.: "Focus on hepatocellular carcinoma", CANCER CELL, vol. 5, 2004, pages 215 - 219
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THIAGALINGAM SCHENG KHLEE HJMINEVA NTHIAGALINGAM APONTE JF, HISTONE DEACETYLASES: UNIQUE PLAYERS IN SHAPING THE EPIGENETIC HISTONE CODE ANN N Y ACAD SCI, vol. 983, 2003, pages 84 - 100
YANG XJSETO E, THE RPD3/HDAL FAMILY OF LYSINE DEACETYLASES: FROM BACTERIA AND YEAST TO MICE AND MEN NAT REV MOL CELL BIOL, vol. 9, 2008, pages 206 - 218
WITT ODEUBZER HEMILDE TOEHME I, HDAC FAMILY: WHAT ARE THE CANCER RELEVANT TARGETS CANCER LETT, vol. 277, 2009, pages 8 - 21
YANG XJSETO E, HATS AND HDACS: FROM STRUCTURE, FUNCTION AND REGULATION TO NOVEL STRATEGIES FOR THERAPY AND PREVENTION ONCOGENE, vol. 26, 2007, pages 5310 - 5318
HUBBERT CGUARDIOLA ASHAO RKAWAGUCHI YITO ANIXON A ET AL.: "HDAC6 is a microtubule-associated Misl8oc", NATURE, vol. 417, 2002, pages 455 - 458
NAT REV DRUG DISCOV., vol. 19, no. 10, October 2020 (2020-10-01), pages 673 - 694
"Remington's Pharmaceutical Sciences", 1990, MACK PUBLISHING COMPANY
"Goodman and Gilman's The Pharmacological Basis of Therapeutics", 2001, PERGAMON PRESS
SEGAL MEIRAV, BISCANS ANNABELLE, GILLES MAUD-EMMANUELLE, ANASTASIADOU ELENI, DE LUCA ROBERTO, LIM JIHOON, KHVOROVA ANASTASIA, SLAC: "Hydrophobically Modified let-7b miRNA Enhances Biodistribution to NSCLC and Downregulates HMGA2 In Vivo", MOLECULAR THERAPY-NUCLEIC ACIDS, CELL PRESS, US, vol. 19, 1 March 2020 (2020-03-01), US , pages 267 - 277, XP093032872, ISSN: 2162-2531, DOI: 10.1016/j.omtn.2019.11.008
CUI HAO, ZHU XINYING, LI SHUYUE, WANG PEIPEI, FANG JIANPING: "Liver-Targeted Delivery of Oligonucleotides with N-Acetylgalactosamine Conjugation", ACS OMEGA, ACS PUBLICATIONS, US, vol. 6, no. 25, 29 June 2021 (2021-06-29), US , pages 16259 - 16265, XP055873459, ISSN: 2470-1343, DOI: 10.1021/acsomega.1c01755
AHN J, FLAMM SL HEPATOCELLULAR CARCINOMA DIS MON, vol. 50, 2004, pages 556 - 573
ROBERTS LRGORES GJ: "Hepatocellular carcinoma: molecular pathways and new therapeutic targets", SEMIN LIVER DIS, vol. 25, 2005, pages 212 - 225
BRUIX J ET AL.: "Focus on hepatocellular carcinoma", CANCER CELL, vol. 5, 2004, pages 215 - 219
SHEN YCHSU CCHENG AL: "Molecular targeted therapy for advanced hepatocellular carcinoma: current status and future perspectives", J GASTROENTEROL, vol. 45, pages 794 - 807, XP037914158, DOI: 10.1007/s00535-010-0270-0
THIAGALINGAM SCHENG KHLEE HJMINEVA NTHIAGALINGAM APONTE JF, HISTONE DEACETYLASES: UNIQUE PLAYERS IN SHAPING THE EPIGENETIC HISTONE CODE ANN N Y ACAD SCI, vol. 983, 2003, pages 84 - 100
YANG XJSETO E, THE RPD3/HDAL FAMILY OF LYSINE DEACETYLASES: FROM BACTERIA AND YEAST TO MICE AND MEN NAT REV MOL CELL BIOL, vol. 9, 2008, pages 206 - 218
WITT ODEUBZER HEMILDE TOEHME I, HDAC FAMILY: WHAT ARE THE CANCER RELEVANT TARGETS CANCER LETT, vol. 277, 2009, pages 8 - 21
YANG XJSETO E, HATS AND HDACS: FROM STRUCTURE, FUNCTION AND REGULATION TO NOVEL STRATEGIES FOR THERAPY AND PREVENTION ONCOGENE, vol. 26, 2007, pages 5310 - 5318
HUBBERT CGUARDIOLA ASHAO RKAWAGUCHI YITO ANIXON A ET AL.: "HDAC6 is a microtubule-associated Misl8oc", NATURE, vol. 417, 2002, pages 455 - 458
NAT REV DRUG DISCOV., vol. 19, no. 10, October 2020 (2020-10-01), pages 673 - 694
"Remington's Pharmaceutical Sciences", 1990, MACK PUBLISHING COMPANY
"Goodman and Gilman's The Pharmacological Basis of Therapeutics", 2001, PERGAMON PRESS
Attorney, Agent or Firm:
WIE, Byoung-Gap (KR)
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